10-119676556-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004281.4(BAG3):c.1002T>G(p.Pro334Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,613,926 control chromosomes in the GnomAD database, including 9,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P334P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.12 ( 1334 hom., cov: 31)

Exomes 𝑓: 0.099 ( 8087 hom. )

Consequence

BAG3
NM_004281.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.879

Publications

16 publications found

Variant links:

Genes affected

BAG3 (HGNC:939): (BAG cochaperone 3) BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The protein encoded by this gene contains a WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. [provided by RefSeq, Jul 2008]

BAG3 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1HH
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
myofibrillar myopathy
Inheritance: AD, Unknown Classification: DEFINITIVE Submitted by: G2P, ClinGen
myofibrillar myopathy 6
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Charcot-Marie-tooth disease, axonal, type 2JJ
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
distal hereditary motor neuropathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BAG3 links:

ENSG00000295480 (HGNC:):

ENSG00000295480 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-119676556-T-G is Benign according to our data. Variant chr10-119676556-T-G is described in ClinVar as Benign. ClinVar VariationId is 44774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.879 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004281.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG3	NM_004281.4	MANE Select	c.1002T>G	p.Pro334Pro	synonymous	Exon 4 of 4	NP_004272.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAG3	ENST00000369085.8	TSL:1 MANE Select	c.1002T>G	p.Pro334Pro	synonymous	Exon 4 of 4	ENSP00000358081.4	O95817
BAG3	ENST00000889977.1		c.1002T>G	p.Pro334Pro	synonymous	Exon 5 of 5	ENSP00000560036.1
BAG3	ENST00000889978.1		c.999T>G	p.Pro333Pro	synonymous	Exon 4 of 4	ENSP00000560037.1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18750

AN:

151934

Hom.:

1329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0833

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.0830

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0879

Gnomad OTH

AF:

0.125

GnomAD2 exomes

AF:

0.118

AC:

29639

AN:

251464

AF XY:

0.111

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.0761

Gnomad EAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.0864

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0985

AC:

144009

AN:

1461874

Hom.:

8087

Cov.:

AF XY:

0.0973

AC XY:

70774

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.166

AC:

5573

AN:

33480

American (AMR)

AF:

0.171

AC:

7663

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0810

AC:

2118

AN:

26136

East Asian (EAS)

AF:

0.264

AC:

10467

AN:

39700

South Asian (SAS)

AF:

0.0821

AC:

7079

AN:

86258

European-Finnish (FIN)

AF:

0.106

AC:

5654

AN:

53410

Middle Eastern (MID)

AF:

0.0796

AC:

459

AN:

5768

European-Non Finnish (NFE)

AF:

0.0887

AC:

98592

AN:

1112002

Other (OTH)

AF:

0.106

AC:

6404

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

8513

17026

25539

34052

42565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3852

7704

11556

15408

19260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.123

AC:

18773

AN:

152052

Hom.:

1334

Cov.:

AF XY:

0.124

AC XY:

9218

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.167

AC:

6910

AN:

41430

American (AMR)

AF:

0.151

AC:

2301

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0833

AC:

289

AN:

3470

East Asian (EAS)

AF:

0.261

AC:

1347

AN:

5166

South Asian (SAS)

AF:

0.0828

AC:

398

AN:

4806

European-Finnish (FIN)

AF:

0.108

AC:

1147

AN:

10598

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0879

AC:

5973

AN:

67990

Other (OTH)

AF:

0.129

AC:

273

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

796

1592

2389

3185

3981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.104

Hom.:

807

Bravo

AF:

0.131

Asia WGS

AF:

0.165

AC:

571

AN:

3478

EpiCase

AF:

0.0843

EpiControl

AF:

0.0836

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Myofibrillar myopathy 6 (2)

not provided (2)

Cardiovascular phenotype (1)

Dilated cardiomyopathy 1HH (1)

Myofibrillar myopathy 6;C3151293:Dilated cardiomyopathy 1HH (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.6

(source)

DANN

Benign

0.71

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over